Perhaps the most devastating and long reaching effects of in utero alcohol exposure is its effect on the central nervous system and the ensuing behavioral dysfunctions that occur. Previous research has demonstrated that the brain may be especially vulnerable to alcohol insult during the third trimester of gestation. During this period, the brain undergoes a period of rapid development, known as the "brain growth spurt" when synaptogenesis, myelination and the formation of glia and microneurons occurs. These same developmental processes occur after birth in the rat, and in order to model human third trimester alcohol exposure, alcohol has to be administered to the neonatal rat. We are using a neonatal administration model, "the-pup-in-the-cup," to assess the influence of alcohol during the third trimester equivalent on various behavioral outcomes. In this project we will continue our investigations of the role of differential alcohol sensitivity as a risk factor for fetal alcohol effects. Not every woman who abuses alcohol gives birth to a child with the fetal alcohol syndrome, and identifying risk factors is an important issue. It has been suggested and data have been reported indicating that differential sensitivity to alcohol may be a significant risk factor. Using rat lines selectively bred for extremes in alcohol induced "sleep time," we will examine various behavioral endpoints known to be sensitive to neonatal alcohol administration. We will also follow-up our findings that the basal ganglia are involved in the behavioral outcomes noted after perinatal alcohol exposure. The basal ganglia are known to be involved in several behaviors (e.g., spatial memory) which are also known to be influenced by perinatal alcohol insult. Using behavioral tasks known to be affected by neonatal basal ganglia damage we should be able to determine if this area is vulnerable to alcohol insult. Finally we will begin investigations into the role of excitotoxicity in alcohol's behavioral teratogenicity. Prenatal alcohol exposure is known to effect NMDA receptors and there is reason to believe that excitotoxicity, either as a result of hypoxia or ethanol withdrawal, may play a significant role in the etiology of fetal alcohol effects. Hopefully, this research will provide us with a clearer understanding of the etiology of and the mechanisms underlying fetal alcohol effects.